EP0554656A1 - Méthode pour la détermination des antigenes ou des anticorps et présence d'un immunocomplexe - Google Patents
Méthode pour la détermination des antigenes ou des anticorps et présence d'un immunocomplexe Download PDFInfo
- Publication number
- EP0554656A1 EP0554656A1 EP93100039A EP93100039A EP0554656A1 EP 0554656 A1 EP0554656 A1 EP 0554656A1 EP 93100039 A EP93100039 A EP 93100039A EP 93100039 A EP93100039 A EP 93100039A EP 0554656 A1 EP0554656 A1 EP 0554656A1
- Authority
- EP
- European Patent Office
- Prior art keywords
- immune complex
- antibodies
- latex
- determination
- antigen
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Granted
Links
Classifications
-
- G—PHYSICS
- G01—MEASURING; TESTING
- G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
- G01N33/00—Investigating or analysing materials by specific methods not covered by groups G01N1/00 - G01N31/00
- G01N33/48—Biological material, e.g. blood, urine; Haemocytometers
- G01N33/50—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing
- G01N33/53—Immunoassay; Biospecific binding assay; Materials therefor
- G01N33/564—Immunoassay; Biospecific binding assay; Materials therefor for pre-existing immune complex or autoimmune disease, i.e. systemic lupus erythematosus, rheumatoid arthritis, multiple sclerosis, rheumatoid factors or complement components C1-C9
-
- G—PHYSICS
- G01—MEASURING; TESTING
- G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
- G01N2800/00—Detection or diagnosis of diseases
- G01N2800/10—Musculoskeletal or connective tissue disorders
- G01N2800/101—Diffuse connective tissue disease, e.g. Sjögren, Wegener's granulomatosis
- G01N2800/102—Arthritis; Rheumatoid arthritis, i.e. inflammation of peripheral joints
-
- Y—GENERAL TAGGING OF NEW TECHNOLOGICAL DEVELOPMENTS; GENERAL TAGGING OF CROSS-SECTIONAL TECHNOLOGIES SPANNING OVER SEVERAL SECTIONS OF THE IPC; TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
- Y10—TECHNICAL SUBJECTS COVERED BY FORMER USPC
- Y10S—TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
- Y10S436/00—Chemistry: analytical and immunological testing
- Y10S436/811—Test for named disease, body condition or organ function
-
- Y—GENERAL TAGGING OF NEW TECHNOLOGICAL DEVELOPMENTS; GENERAL TAGGING OF CROSS-SECTIONAL TECHNOLOGIES SPANNING OVER SEVERAL SECTIONS OF THE IPC; TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
- Y10—TECHNICAL SUBJECTS COVERED BY FORMER USPC
- Y10S—TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
- Y10S530/00—Chemistry: natural resins or derivatives; peptides or proteins; lignins or reaction products thereof
- Y10S530/81—Carrier - bound or immobilized peptides or proteins and the preparation thereof, e.g. biological cell or cell fragment as carrier
- Y10S530/812—Peptides or proteins is immobilized on, or in, an organic carrier
Definitions
- the invention relates to an immunochemical method for the detection and determination of rheumatoid factors using immune complexes as specific binding partners, and to the preparation of reagents suitable for these methods.
- Serological examination methods have found wide application in rheumatological diagnosis. Serums are examined for the presence of antibodies that the body forms against the body's own substances in the case of these diseases; these antibodies are therefore also referred to as "autoantibodies”.
- Rheumatoid factors are antibodies against the body's own immunoglobulins, i.e. anti-immunoglobulin antibodies, and anti-nuclear antibodies are autoantibodies against structures in the body's own cell nuclei.
- Rheumatoid factors occur in all immunoglobulin classes, they mostly belong to the immunoglobulin classes IgM, IgG and IgA.
- rheumatoid factors are based on the agglutination of, for example, erythrocytes or latex particles which are mixed with human or animal IgG are coated. These methods only allow a qualitative or semi-quantitative determination of rheumatoid factors and the reading of the results of these agglutination tests is subjective, due to the visual evaluation.
- nephelometric or turbidimetric methods are used to determine rheumatoid factors.
- the light scatter and thus the sensitivity of the nephelometric or turbidimetric method depends on the "particle size" of the antigen or the antibody.
- a known method is to bind a human immunoglobulin to latex particles that themselves scatter the light.
- radio and enzyme immunoassays also allow differentiation of the rheumatoid factor classes IgM, IgG and IgA. However, they are very labor intensive and the determination takes several hours.
- an immune complex of antibodies against human IgG from sheep and human IgG or an immune complex of antibodies against human gamma globulin from rabbit and human gamma globulin are used.
- the immune complexes are bound to latex particles by known methods.
- the latex reagent obtained can be used in the manual latex agglutination test or in nephelometric or turbidimetric methods using kinetic or end point methods.
- the invention accordingly relates to an immunochemical method for the detection and determination of rheumatoid factors (analyte) by means of a specific binding partner, this being an immune complex.
- a method is preferred in which the immune complex was produced from antisera from immunized animals with an antigen of human, animal or vegetable origin that is not the analyte.
- a method in which the immune complex is bound to a solid phase is very particularly preferred.
- An antiserum from sheep or rabbit is preferably used.
- a method as described above is also preferred, the evaluation being carried out according to a particle-reinforced immunological method.
- the invention also relates to a process for the preparation of an immune complex for use in the process described without, the immune complex being prepared in an aqueous solution in the presence of up to 50% by volume of a cyclic amide, preferably in the presence of gamma-amino-butyrolactam.
- the latex particles can be loaded by adsorption or by covalent binding of proteins.
- Latex derivatives with the free carboxyl groups, amino groups, aldehyde groups and epoxy groups as well as vicinal hydroxyl groups can be used for covalent bonding.
- the latices which can be used to prepare the reagent according to the invention can be obtained, for example, by polymerizing olefinically unsaturated monomers.
- Styrene copolymers such as styrene-butadiene copolymers and acrylonitrile-butadiene-styrene copolymers, vinyl acetate-acrylate copolymers or vinyl chloride-acrylate copolymers are preferred.
- Polystyrene latex suspensions or emulsions of suitable particle size can also be obtained under various trade names from a number of manufacturers.
- Mono- and polydisperse latex suspensions are suitable.
- the immune complexes can be prepared by known methods by mixing the antigen with the specific antibody.
- Specific antisera, gamma globulin fractions from antisera, immunoadsorptively purified antibodies or monoclonal antibodies are suitable.
- Sera and gamma globulin fractions from antisera which already contain immune complexes through the immunization of animals are also suitable.
- Examples of immune complexes are human IgG / antiserum against human IgG from sheep, human gamma globulin / antiserum against human gamma globulin from rabbit.
- the ratio of antigen / antibody in the immune complex depends on the antibody content and is 1: 0.05 - 5, preferably 0.05: 2, most preferably about 1: 0.1.
- the invention thus also relates to a process for the preparation of the immune complexes used in the process. Since a precipitant such as polyethylene glycol (PEG) is usually used in the particle-reinforced agglutination method, the complexes must not be precipitated by the precipitant. In addition, they must be stable in storage over a longer period, that is to say usually at least 3 months, preferably at least 12 months.
- a precipitant such as polyethylene glycol (PEG)
- PEG polyethylene glycol
- the complex is prepared in an aqueous solution, preferably in the presence of a polar solvent which is readily miscible with water, such as dimethyl sulfoxide and dimethylformamide.
- a polar solvent which is readily miscible with water, such as dimethyl sulfoxide and dimethylformamide.
- the complexes are preferably prepared in the presence of a cyclic amide, and pyrrolidone (gamma-amino-butyrolactam) is particularly suitable.
- the immune complexes prepared in this way are stable in storage in aqueous solutions for at least 3, preferably at least 12 months.
- the latex particles can be loaded with the immune complex by a method known to the person skilled in the art. It can e.g. B. can be loaded as follows:
- An immune complex produced from an antiserum / antigen is mixed with a suspension of the latex particles with a concentration of about 50 to 200, preferably 100 g / l, and 0.5 - 5 hours at a temperature between 0 and +60 ° C., preferably Incubated +20 - +60 ° C.
- the portion of the immune complex that is not bound to latex particles can be removed by centrifugation and resuspension of the solid.
- the reagent can be resuspended in a buffer solution, preferably glycine-NaCl buffer of pH 7-8.5, to which a protein, for example human albumin or bovine albumin, can optionally be added.
- the immune complex is placed in a glycine-NaCl buffer, optionally stabilized with human or bovine serum albumin and with a 0.5 to 2% polystyrene latex suspension until To achieve the desired sensitivity.
- the reagent thus prepared can be stored at +4 ° C or lyophilized.
- the antisera which can be used to produce the antibody are obtained by immunizing animals, in particular rabbits, sheep and goats, with proteins of human, animal or vegetable origin. Examples are: rabbit anti-human IgG serum, rabbit anti-human gamma globulin, sheep anti-rabbit gamma globulin serum, sheep anti-human IgG serum.
- the anti-human IgG serum from sheep and anti-human gamma globulin serum from rabbit are particularly suitable.
- the immunization was carried out according to known methods. The immunization dose and time depend on the immunogenicity and the molecular weight of the protein.
- Monoclonal antibodies can also be used as antibodies in the sense of this invention.
- the patient sera to be determined were diluted in phosphate-saline buffer.
- the results were then measured on a nephelometer (Behringwerke AG, Marburg).
- the measuring range was 9 to 560 IU / ml with a 1:20 serum dilution and 45 to 7000 IU / ml with a 1: 100 serum dilution.
- the table shows the very good recovery and fastness to dilution of the determination of the rheumatoid factors according to the invention.
- the following table shows a comparison of RF values that were determined using the Immukomplex ELISA and a quantitative RF test based on the current state of the art: Serum no. ELISA RF / IgM (IU / ml) Nephelometric RF determination (IU / ml) 1 236 228 2nd 65 84 3rd 101 104 4th 42 52 5 62 60 6 16 21
Landscapes
- Health & Medical Sciences (AREA)
- Immunology (AREA)
- Life Sciences & Earth Sciences (AREA)
- Hematology (AREA)
- Engineering & Computer Science (AREA)
- Molecular Biology (AREA)
- Chemical & Material Sciences (AREA)
- Biomedical Technology (AREA)
- Urology & Nephrology (AREA)
- Food Science & Technology (AREA)
- Biochemistry (AREA)
- Cell Biology (AREA)
- Biotechnology (AREA)
- Rheumatology (AREA)
- Rehabilitation Therapy (AREA)
- Medicinal Chemistry (AREA)
- Physics & Mathematics (AREA)
- Analytical Chemistry (AREA)
- Microbiology (AREA)
- General Health & Medical Sciences (AREA)
- General Physics & Mathematics (AREA)
- Pathology (AREA)
- Medicines Containing Antibodies Or Antigens For Use As Internal Diagnostic Agents (AREA)
- Investigating Or Analysing Biological Materials (AREA)
- Peptides Or Proteins (AREA)
- Electrical Discharge Machining, Electrochemical Machining, And Combined Machining (AREA)
- Paper (AREA)
- Input Circuits Of Receivers And Coupling Of Receivers And Audio Equipment (AREA)
- Exchange Systems With Centralized Control (AREA)
Applications Claiming Priority (2)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
DE4202924A DE4202924A1 (de) | 1992-02-01 | 1992-02-01 | Verfahren zur bestimmung von rheumafaktoren und mittel zur durchfuehrung des verfahrens |
DE4202924 | 1992-02-01 |
Publications (2)
Publication Number | Publication Date |
---|---|
EP0554656A1 true EP0554656A1 (fr) | 1993-08-11 |
EP0554656B1 EP0554656B1 (fr) | 1999-07-14 |
Family
ID=6450791
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
EP93100039A Expired - Lifetime EP0554656B1 (fr) | 1992-02-01 | 1993-01-05 | Méthode et moyens pour la détermination des facteurs rhumatoides |
Country Status (8)
Country | Link |
---|---|
US (1) | US5989922A (fr) |
EP (1) | EP0554656B1 (fr) |
JP (1) | JP3220545B2 (fr) |
AT (1) | ATE182215T1 (fr) |
AU (1) | AU667700B2 (fr) |
CA (1) | CA2088471C (fr) |
DE (2) | DE4202924A1 (fr) |
ES (1) | ES2135421T3 (fr) |
Families Citing this family (3)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
DE4202923A1 (de) * | 1992-02-01 | 1993-08-05 | Behringwerke Ag | Verfahren zur bestimmung von antigenen oder antikoerpern in gegenwart eines immunkomplexes |
GB0803107D0 (en) * | 2008-02-20 | 2008-03-26 | Axis Shield Diagnostics Ltd | Method |
USD939079S1 (en) | 2019-08-22 | 2021-12-21 | Icu Medical, Inc. | Infusion pump |
Citations (5)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
EP0019741A1 (fr) * | 1979-05-07 | 1980-12-10 | BEHRINGWERKE Aktiengesellschaft | Réactif de latex, procédé pour sa préparation, son utilisation et préparation contenant ce réactif |
EP0044041A1 (fr) * | 1980-07-14 | 1982-01-20 | Hoechst Aktiengesellschaft | Méthode pour la liaison et la séparation dans les radioimmunoessais compétitifs et réactif pour cette méthode |
EP0087728A1 (fr) * | 1982-02-25 | 1983-09-07 | BEHRINGWERKE Aktiengesellschaft | Procédé immunologique pour l'agglutination du latex |
US4547466A (en) * | 1983-06-01 | 1985-10-15 | Allied Corporation | Detecting rheumatoid factor with synthetic particles having immune complexes thereon |
EP0353306A1 (fr) * | 1988-01-12 | 1990-02-07 | Toyo Boseki Kabushiki Kaisha | Element de depistage du facteur rhumatoide et procede d'analyse |
Family Cites Families (7)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
CA1146852A (fr) * | 1979-01-31 | 1983-05-24 | Koichi Kondo | Reactif d'agglutination du latex |
US4590156A (en) * | 1982-05-21 | 1986-05-20 | The University Of Tennessee Research Corporation | Agglutination assay and product for rubella antibody |
DE3303083A1 (de) * | 1983-01-31 | 1984-08-02 | Behringwerke Ag, 3550 Marburg | Immunologisches latex-agglutinationsverfahren und mittel |
US4935339A (en) * | 1985-05-07 | 1990-06-19 | Nichols Institute Diagnostics | Delayed solid phase immunologic assay |
US4670381A (en) * | 1985-07-19 | 1987-06-02 | Eastman Kodak Company | Heterogeneous immunoassay utilizing horizontal separation in an analytical element |
JPS63235868A (ja) * | 1987-03-24 | 1988-09-30 | Nitto Electric Ind Co Ltd | リウマチ因子定量法 |
JPH02259569A (ja) * | 1989-03-31 | 1990-10-22 | Nitto Denko Corp | リウマチ因子測定方法 |
-
1992
- 1992-02-01 DE DE4202924A patent/DE4202924A1/de not_active Withdrawn
-
1993
- 1993-01-05 EP EP93100039A patent/EP0554656B1/fr not_active Expired - Lifetime
- 1993-01-05 ES ES93100039T patent/ES2135421T3/es not_active Expired - Lifetime
- 1993-01-05 DE DE59309692T patent/DE59309692D1/de not_active Expired - Lifetime
- 1993-01-05 AT AT93100039T patent/ATE182215T1/de not_active IP Right Cessation
- 1993-01-29 AU AU32118/93A patent/AU667700B2/en not_active Ceased
- 1993-01-29 CA CA002088471A patent/CA2088471C/fr not_active Expired - Fee Related
- 1993-01-29 JP JP01301193A patent/JP3220545B2/ja not_active Expired - Fee Related
-
1994
- 1994-09-22 US US08/310,042 patent/US5989922A/en not_active Expired - Lifetime
Patent Citations (5)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
EP0019741A1 (fr) * | 1979-05-07 | 1980-12-10 | BEHRINGWERKE Aktiengesellschaft | Réactif de latex, procédé pour sa préparation, son utilisation et préparation contenant ce réactif |
EP0044041A1 (fr) * | 1980-07-14 | 1982-01-20 | Hoechst Aktiengesellschaft | Méthode pour la liaison et la séparation dans les radioimmunoessais compétitifs et réactif pour cette méthode |
EP0087728A1 (fr) * | 1982-02-25 | 1983-09-07 | BEHRINGWERKE Aktiengesellschaft | Procédé immunologique pour l'agglutination du latex |
US4547466A (en) * | 1983-06-01 | 1985-10-15 | Allied Corporation | Detecting rheumatoid factor with synthetic particles having immune complexes thereon |
EP0353306A1 (fr) * | 1988-01-12 | 1990-02-07 | Toyo Boseki Kabushiki Kaisha | Element de depistage du facteur rhumatoide et procede d'analyse |
Non-Patent Citations (2)
Title |
---|
DATABASE WPIL Section Ch, Week 8514, Derwent Publications Ltd., London, GB; Class A96, AN 85-084828 & JP-A-60 036 966 (EIKEN KAGAKU KK) 26. Februar 1985 * |
DATABASE WPIL Section Ch, Week 8845, Derwent Publications Ltd., London, GB; Class B04, AN 88-319016 & JP-A-63 235 868 (NITTO ELECTRIC IND. KK) 30. September 1988 * |
Also Published As
Publication number | Publication date |
---|---|
AU3211893A (en) | 1993-08-05 |
JPH05281234A (ja) | 1993-10-29 |
AU667700B2 (en) | 1996-04-04 |
CA2088471C (fr) | 2004-06-22 |
DE4202924A1 (de) | 1993-08-05 |
US5989922A (en) | 1999-11-23 |
DE59309692D1 (de) | 1999-08-19 |
ES2135421T3 (es) | 1999-11-01 |
EP0554656B1 (fr) | 1999-07-14 |
JP3220545B2 (ja) | 2001-10-22 |
ATE182215T1 (de) | 1999-07-15 |
CA2088471A1 (fr) | 1993-08-02 |
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